D-Gluconic acid, 2,3,4,6-tetrakis-O-(trimethylsilyl)-, .delta.-lactone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 July - 16 August 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(3R,4S,5R,6R)-3,4,5-tris[(trimethylsilyl)oxy]-6-{[(trimethylsilyl)oxy]methyl}oxan-2-one

EC Number:

608-732-8

Cas Number:

32384-65-9

Molecular formula:

C18 H42 O6 Si4

IUPAC Name:

(3R,4S,5R,6R)-3,4,5-tris[(trimethylsilyl)oxy]-6-{[(trimethylsilyl)oxy]methyl}oxan-2-one

Test material form:

liquid

Test animals

Species:

rat

Strain:

other: Crl:WI(Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Male and Female Crl:WI(Han), SPF quality strain rats were obtained from Charles River Laboratories
- The rats were in a body weight range of 172 g-178 g for Males and 163 g-167 g for Females on Day 1.
- Rats were approximately 8 weeks old on Day 1

CONDITIONS
- Municipal tap drinking water (Stadtwerke Biberach) was available ad libitum via drinking bottles.
- The animals received pelleted dry food (Kliba No. 3438. PM.BB1, Provimi Kliba SA,
CH-4303 Kaiseraugst, Switzerland (see paragraph 2.8, study plan deviation 3). Food was
available ad libitum but was withdrawn in the afternoon of Day -1 over night. Immediately
post administration, free access to food was allowed again.
- The animal rooms were designed to permit approximately of 10 air changes per hour. The target temperature and relative humidity ranges were 22 °C ± 2 °C and 45 % - 75 %, respectively.
- Light/darkness cycle: 12/12 hours

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % aqueous hydroxyethylcellulose (Natrosol® 250 HX)

Details on oral exposure:

Oral administration of BI 10773 TMS-LACTON formulation by gavage was conducted.

Doses:

300 and 2000mg/kg

No. of animals per sex per dose:

3 females per 300 mg/kg
3 males per 2000 mg/kg
3 females per 2000 mg/kg

Control animals:

no

Details on study design:

Clinical signs were evaluated frequently after dosing on Day 1 and once or twice daily until
the day of necropsy. Body weight was recorded on Day -1, Day 1 before administration and
during the observation period on Day 2, 8 and 15. At the end of the observation period,
necropsy was performed on all animals, and all gross macroscopical changes were recorded

The animals were observed for a period of 14 days post administration (p.a.).

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

> 300 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was noted.

Clinical signs:

other: No toxicologically relevant signs of toxicity were observed. In male animals (No. 301 to 303) administered 2000 mg/kg transiently decreased locomotor activity was observed on Day 1 at 4 h post administration.

Gross pathology:

No macroscopic changes were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

other: not classified acc. CLP

Conclusions:

Under the conditions of the present study, a single oral administration (gavage) of
BI 10773 TMS-LACTON at doses of 300 (females) and 2000 mg/kg (males and females) was
associated with no signs of toxicity and no deaths. Thus, the approximate lethal dose (ALD)
is above 2000 mg/kg in male and female rats.